Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with ...non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade.
We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD.
A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868–7.440 and overall survival (HR, 5.079; 95% CI, 3.136–8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7−CD45RA− T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate.
HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.
Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making ...magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.
The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 ... GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.
Out-of-time ordered (OTO) correlation functions describe scrambling of information in correlated quantum matter. They are of particular interest in incoherent quantum systems lacking well defined ...quasi-particles. Thus far, it is largely elusive how OTO correlators spread in incoherent systems with diffusive transport governed by a few globally conserved quantities. Here, we study the dynamical response of such a system using high-performance matrix-product-operator techniques. Specifically, we consider the non-integrable, one-dimensional Bose-Hubbard model in the incoherent high-temperature regime. Our system exhibits diffusive dynamics in time-ordered correlators of globally conserved quantities, whereas OTO correlators display a ballistic, light-cone spreading of quantum information. The slowest process in the global thermalization of the system is thus diffusive, yet information spreading is not inhibited by such slow dynamics. We furthermore develop an experimentally feasible protocol to overcome some challenges faced by existing proposals and to probe time-ordered and OTO correlation functions. Our study opens new avenues for both the theoretical and experimental exploration of thermalization and information scrambling dynamics.
Foamed and solid polypropylene/carbon fiber (PP–CF) composites containing various CF contents (0–10vol.%) were injection-molded. Foamed composites were achieved using dissolved pressurized nitrogen ...gas. The effects of foaming on the fibers inter-connectivity and orientation, electrical percolation threshold, through-plane electrical conductivity, longitudinal and transversal in-plane conductivities, dielectric permittivity, and electromagnetic interference (EMI) shielding effectiveness (SE) were investigated. Cell growth increased the fibers inter-connectivity by biaxial stretching of the matrix and also changed the fiber orientation. The introduction of foaming reduced the density of the injection-molded samples by 25%, lowered the volume fraction of the percolation threshold from 8.5 to 7vol.% CF, enhanced the through-plane conductivity up to a maximum of six orders of magnitude, increased the dielectric permittivity and resulted in the increase of the specific EMI SE up to 65%. Moreover, the uniformity of in-plane and through-plane conductivities as well as EMI SE along the injection-molded samples was greatly improved by foaming. The relationships between the microstructure and electrical properties were also established. The results reveal that lightweight conductive products with lower fiber content and enhanced electrical and EMI shielding properties can be fabricated with the aid of injection foam molding for applications in electronics, aerospace and automotive industries.
Nano/microcellular polypropylene/multiwalled carbon nanotube (MWCNT) composites exhibiting higher electrical conductivity, lower electrical percolation, higher dielectric permittivity, and lower ...dielectric loss are reported. Nanocomposite foams with relative densities (ρR) of 1.0–0.1, cell sizes of 70nm–70μm, and cell densities of 3×107–2×1014 cellscm−3 are achieved, providing a platform to assess the evolution of electrical properties with foaming degree. The electrical percolation threshold decreases more than fivefold, from 0.50 down to 0.09vol.%, as the volume expansion increases through foaming. The electrical conductivity increases up to two orders of magnitude in the nanocellular nanocomposites (1.0>ρR>∼0.6). In the proper microcellular range (ρR≈0.45), the introduction of cellular structure decreases the dielectric loss up to five orders of magnitude, while the decrease in dielectric permittivity is only 2–4 times. Thus, microcellular composites containing only ∼0.34vol.% MWCNT present a frequency-independent high dielectric permittivity (∼30) and very low dielectric loss (∼0.06). The improvements in such properties are correlated to the microstructural evolution caused by foaming action (biaxial stretching) and volume exclusion. High conductivity foams have applications in electromagnetic shielding and high dielectric foams can be developed for charge storage applications.
We present results from an analysis of all data taken by the bicep2/Keck CMB polarization experiments up to and including the 2015 observing season. This includes the first Keck Array observations at ...220 GHz and additional observations at 95 and 150 GHz. The Q and U maps reach depths of 5.2, 2.9, and 26 μK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈400 square degrees. The 220 GHz maps achieve a signal to noise on polarized dust emission approximately equal to that of Planck at 353 GHz. We take auto and cross spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz. We evaluate the joint likelihood of the spectra versus a multicomponent model of lensed-ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and we impose priors on some of these using external information from Planck and WMAP derived from larger regions of sky. The model is shown to be an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.07 at 95% confidence, which tightens to r_{0.05}<0.06 in conjunction with Planck temperature measurements and other data. The lensing signal is detected at 8.8σ significance. Running a maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.020. These are the strongest constraints to date on primordial gravitational waves.
We combine Spitzer and ground-based Korea Microlensing Telescope Network microlensing observations to identify and precisely measure an Earth-mass ( ) planet OGLE-2016-BLG-1195Lb at orbiting a ...ultracool dwarf. This is the lowest-mass microlensing planet to date. At kpc, it is the third consecutive case among the Spitzer "Galactic distribution" planets toward the Galactic bulge that lies in the Galactic disk as opposed to the bulge itself, hinting at a skewed distribution of planets. Together with previous microlensing discoveries, the seven Earth-size planets orbiting the ultracool dwarf TRAPPIST-1, and the detection of disks around young brown dwarfs, OGLE-2016-BLG-1195Lb suggests that such planets might be common around ultracool dwarfs. It therefore sheds light on the formation of both ultracool dwarfs and planetary systems at the limit of low-mass protoplanetary disks.
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